The E2F family of transcription factors regulates gene expression following heterodimerization with the DP family proteins, which promote transition to S phase from G1 phase. E2F activity is controlled by interactions with the retinoblastoma tumor suppressor family (pRB, p107 and p130). E2F proteins can be divided into three groups on homology and on certain functional characteristics. The first group containing E2F-1, E2F-2 and E2F-3 binds exclusively to pRB and has a cyclin A binding domain that mediates inhibition of DNA binding during entry into S phase. The second group is composed of E2F-4 and E2F-5, which preferentially bind to p107 and p130, although they can bind pRB as well. The last member is E2F-6. E2F-6 appears to act as a transcription repressor. E2F-4 and E2F-5 are functionally different from E2F-1 and E2F-3. E2F-1 and E2F-3 participate in cellular proliferation, whereas E2F-4 and E2F-5 are required for cell cycle arrest in G1 induced by cyclin-dependent kinase inhibitor p16INK4a.